Empagliflozin and CPAP in Adults With Heart Failure and Obstructive Sleep Apnea. (HF(L)OSA)

Effects of Empagliflozin and Continuous Positive Airway Pressure on Sleep, Cardiac Function, Oxidative Stress Markers, and Patient-Reported Outcomes in Adults With Heart Failure and Obstructive Sleep Apnea: A Randomized Controlled Clinical Trial.

The goal of this randomized clinical trial was to evaluate the effects of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i) on sleep and cardiac outcomes in adults with heart failure (HF) and obstructive sleep apnea syndrome (OSA). The study also examined how subsequent initiation of continuous positive airway pressure (CPAP) therapy affected sleep and cardiac outcomes, and whether response to treatment differed according to baseline obstructive sleep apnea severity.

The main questions it aims to answer were:

• Does empagliflozin affect sleep apnea severity and nocturnal oxygenation before CPAP initiation?
• Does prior empagliflozin treatment influence the response to subsequent CPAP therapy?
• Does empagliflozin affect oxidative stress markers, including total oxidative status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI)?
• Does CPAP therapy initiation affect cardiac outcomes in both groups?
• Does response to treatment differ according to baseline obstructive sleep apnea severity, including mild, moderate, and severe disease?

Researchers compared participants receiving empagliflozin in addition to background HF therapy with those continuing background HF therapy without empagliflozin to evaluate the effects of empagliflozin.

Participants:

• Were randomly assigned to receive empagliflozin plus background HF pharmacotherapy or background HF pharmacotherapy therapy without empagliflozin
• Underwent sleep studies, transthoracic echocardiography and clinical assessments at baseline, 3 months, and 6 months.
• Provided blood samples for measurement of cardiac biomarkers and oxidative stress markers.
• Completed standardized questionnaires assessing sleep quality and symptoms.
• Initiated CPAP therapy after 3 months and continued treatment until the end of the study.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Obstructive Sleep Apnea (OSA); Sleep Apnea Syndrome, Obstructive
• Intervention / Treatment: Drug: Empagliflozin; Device: Continuous Positive Airway Pressure (CPAP)

Detailed Description

Heart failure and obstructive sleep apnea frequently coexist and are linked through complex pathophysiological mechanisms, including intermittent hypoxemia, sympathetic activation, oxidative stress, and hemodynamic alterations. This bidirectional interaction contributes to disease progression, impaired quality of life, and adverse clinical outcomes. While CPAP remains the standard treatment for OSA, treatment response in patients with coexisting HF is variable, and additional therapeutic strategies targeting both conditions are of clinical interest.

Sodium-glucose cotransporter-2 inhibitors, including empagliflozin, have demonstrated significant cardiovascular benefits in patients with HF. Their mechanisms of action, including osmotic diuresis, reduction in intravascular and interstitial fluid volume, and improvement in cardiac function, may also influence the pathophysiology of OSA, particularly by reducing nocturnal rostral fluid shift and upper airway collapsibility. However, prospective randomized data evaluating the effects of SGLT2i on sleep-disordered breathing in patients with HF and OSA remain limited.

This randomized controlled clinical trial was designed to evaluate the effects of empagliflozin on sleep, cardiac, and biochemical outcomes in adults with coexisting HF and OSA, and to assess the impact of subsequent CPAP therapy. The study incorporated a sequential two-phase design to allow differentiation between the early effects of pharmacological therapy and the later effects of CPAP.

In the first phase (0-3 months), participants were randomly assigned in a 1:1 ratio to receive empagliflozin in addition to background HF therapy or to continue background HF therapy without empagliflozin. This phase was designed to evaluate the isolated effect of empagliflozin on OSA severity, nocturnal oxygenation, cardiac function, and oxidative stress.

In the second phase (3-6 months), CPAP therapy was initiated in all participants, while empagliflozin treatment was continued in the study group. This phase was designed to assess the effect of CPAP therapy in both groups and to explore whether prior exposure to empagliflozin influenced the response to CPAP.

Assessments were performed at baseline, 3 months, and 6 months. Sleep-related outcomes included apnea-hypopnea index (AHI), mean oxygen saturation (MOS), lowest oxygen saturation (LOS), and time spent with oxygen saturation below 90% (T<90%), obtained from type III sleep studies. Cardiac outcomes included left ventricular ejection fraction assessed by transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide concentrations. Biochemical analyses included evaluation of oxidative stress markers, including TOS, TAS, and OSI. Patient-reported outcomes included validated questionnaires assessing sleep quality, daytime sleepiness, and quality of life.

The study also included exploratory analyses to assess relationships between sleep-related and cardiac parameters, as well as to evaluate whether baseline OSA severity influenced response to treatment. The sequential design of the study allowed assessment of phase-specific effects and potential interaction between pharmacological therapy and CPAP.

Overall, the study aimed to provide a comprehensive evaluation of the role of empagliflozin as an adjunctive therapy in patients with HF and OSA, and to clarify its potential impact on sleep-disordered breathing, cardiac function, and oxidative stress in the context of subsequent CPAP treatment.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-276
      • University Clinical Hospital in Białystok

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosed heart failure (HF) on stable guideline-directed medical therapy
• Obstructive sleep apnea (OSA) confirmed by sleep study (mild, moderate, or severe)
• No prior treatment with empagliflozin or other sodium-glucose cotransporter-2 inhibitors
• No prior treatment with continuous positive airway pressure therapy
• Body mass index (BMI) <40 kg/m²
• Clinical eligibility for CPAP therapy according to current recommendations
• Ability to provide written informed consent

Exclusion Criteria:

• Age <18 years
• Body mass index (BMI) ≥40 kg/m²
• Active malignancy
• Severe renal impairment (estimated glomerular filtration rate <25 mL/min/1.73 m²)
• Advanced hepatic insufficiency
• Symptomatic hypotension
• Clinically significant volume depletion or dehydration
• Known hypersensitivity to empagliflozin or any component of the study medication
• Any condition that, in the opinion of the investigator, could interfere with study participation or interpretation of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin + Background Heart Failure Therapy; Participants with HF and OSA initiated empagliflozin at baseline in addition to background heart failure therapy and continued treatment throughout the 6-month study period. During the first phase (0-3 months), the effects of empagliflozin were assessed. Continuous positive airway pressure therapy was initiated after 3 months and continued until the end of the study. This design allowed evaluation of the isolated effect of empagliflozin before CPAP initiation and assessment of its influence on response to subsequent CPAP therapy.	Drug: Empagliflozin; Empagliflozin was initiated at baseline at a dose of 10 mg once daily, administered orally, in addition to background heart failure therapy, and continued throughout the 6-month study period.; Device: Continuous Positive Airway Pressure (CPAP); Continuous positive airway pressure therapy was initiated after 3 months in all participants using standard clinical practice. CPAP was applied nightly during sleep, with pressure settings individually titrated. The mean therapeutic pressure was approximately 15.5 ± 2.5 cm H₂O. Treatment was continued until the end of the study.
Active Comparator: Background Heart Failure Therapy Without Empagliflozin; Participants continued background heart failure therapy without empagliflozin. Continuous positive airway pressure (CPAP) therapy was initiated after 3 months and continued until the end of the study. This design allowed evaluation of the isolated effect of empagliflozin before CPAP initiation and assessment of its influence on response to subsequent CPAP therapy.	Device: Continuous Positive Airway Pressure (CPAP); Continuous positive airway pressure therapy was initiated after 3 months in all participants using standard clinical practice. CPAP was applied nightly during sleep, with pressure settings individually titrated. The mean therapeutic pressure was approximately 15.5 ± 2.5 cm H₂O. Treatment was continued until the end of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Apnea-Hypopnea Index (AHI).	Change in AHI, measured as the number of apnea and hypopnea events per hour of sleep, assessed between baseline and follow-up visits at 3 and 6 months.	Baseline, 3 months, and 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.	Change in NT-proBNP concentrations (pg/mL) measured in serum between baseline and follow-up visits.	Baseline, 3 months, and 6 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in nocturnal oxygenation - mean oxygen saturation (MOS).	Change in mean oxygen saturation (%) measured during sleep studies.	Baseline to 3 months and 6 months.
Change in nocturnal oxygenation - lowest oxygen saturation (LOS).	Change in lowest oxygen saturation (%) measured during sleep studies.	Baseline to 3 months and 6 months.
Change in nocturnal oxygenation - time spent with oxygen saturation below 90% (T<90%).	Change in the percentage of time spent with oxygen saturation below 90% during sleep.	Baseline to 3 months and 6 months.
Change in left ventricular ejection fraction (LVEF).	Change in left ventricular ejection fraction (%) assessed by transthoracic echocardiography.	Baseline, 3 months, and 6 months.
Change in total oxidative status (TOS).	Change in total oxidative status ((µmol H₂O₂ equivalent/L) measured in serum.	Baseline, 3 months, and 6 months.
Change in total antioxidant status (TAS).	Change in total antioxidant status (mmol Trolox equivalent/L) measured in serum.	Baseline, 3 months, and 6 months.
Change in oxidative stress index (OSI).	Change in oxidative stress index (arbitrary units) calculated as the ratio of TOS to TAS.	Baseline, 3 months, and 6 months.
Change in Epworth Sleepiness Scale (ESS) score.	Change in daytime sleepiness assessed using the Epworth Sleepiness Scale (points).	Baseline, 3 months, and 6 months.
Change in Pittsburgh Sleep Quality Index (PSQI) score.	Change in sleep quality assessed using the Pittsburgh Sleep Quality Index (points).	Baseline, 3 months, and 6 months.
Change in Short Form-36 (SF-36) score.	Change in quality of life assessed using the Short Form-36 questionnaire (points).	Baseline, 3 months, and 6 months.
Change in snoring severity (VAS).	Change in snoring severity assessed using a visual analogue scale (points).	Baseline, 3 months, and 6 months.
Change in heart failure symptom score.	Change in heart failure symptom burden assessed using a structured symptom score (points).	Baseline, 3 months, and 6 months.

Collaborators and Investigators

• Sponsor: Medical University of Bialystok

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2023
• Primary Completion (Actual): May 9, 2025
• Study Completion (Actual): May 9, 2025

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: sleep; apnea; obstructive sleep apnea; heart failure; heart; sleep apnea
• Additional Relevant MeSH Terms: Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heart Failure; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Therapeutics; Airway Management; Respiratory Therapy; Positive-Pressure Respiration; Respiration, Artificial; empagliflozin; Continuous Positive Airway Pressure
• Other Study ID Numbers: APK.002.526.2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It is not yet determined whether individual participant data will be made available. Data sharing plans will be considered after completion of primary and secondary analyses and publication of study results, in accordance with institutional policies and applicable regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No